tbuckley/cabot-search huggingface dataset:
Utilizing 4D Printing to Design Smart Gastroretentive, Esophageal, and Intravesical Drug Delivery Systems
Authors: Dina B. Mahmoud, Michaela Schulz‐Siegmund
Journal: Advanced Healthcare Materials (2022)

The breakthrough of 3D printing in biomedical research has paved the way for the next evolutionary step referred to as four dimensional (4D) printing. This new concept utilizes the time as the fourth dimension in addition to the x, y, and z axes with the idea to change the configuration of a printed construct with time usually in response to an external stimulus. This can be attained through the incorporation of smart materials or through a preset smart design. The 4D printed constructs may be designed to exhibit expandability, flexibility, self-folding, self-repair or deformability. This review focuses on 4D printed devices for gastroretentive, esophageal, and intravesical delivery. The currently unmet needs and challenges for these application sites are tried to be defined and reported on published solution concepts involving 4D printing. In addition, other promising application sites that may similarly benefit from 4D printing approaches such as tracheal and intrauterine drug delivery are proposed.
Engineering Lipid Spherulites for the Sustained Release of Highly Dosed Small Hydrophilic Compounds
Authors: Elita Montanari, Hanna Krupke, Jean‐Christophe Leroux
Journal: Advanced Healthcare Materials (2022)

Currently, there is a lack of parenteral sustained release formulations for the delivery of highly dosed small hydrophilic drugs. Therefore, parenteral lipid spherulites are engineered capable of entrapping large amounts of such compounds and spontaneously releasing them in a sustained fashion. A library of spherulites is prepared with a simple green process, using phosphatidylcholine (PC) and/or phosphatidylethanolamine (PE), nonionic surfactants and water. The vesicle formulations exhibiting appropriate size distribution and morphology are selected and loaded with 4,6-di-O-(methoxy-diethyleneglycol)-myo-inositol-1,2,3,5-tetrakis(phosphate), ((OEG
Nightmares and psychiatric symptoms: A systematic review of longitudinal, experimental, and clinical trial studies
Authors: Bryony Sheaves, Stephanie Rek, Daniel Freeman
Journal: Clinical Psychology Review (2022)

Nightmares occur across a wide range of psychiatric disorders, but outside of PTSD presentations are infrequently considered a treatment priority. We aimed to assess evidence for a contributory causal role of nightmares to the occurrence of psychiatric disorders, and vice versa. A systematic review was conducted of longitudinal, experimental, and clinical trial studies. Twenty-four longitudinal, sixteen trials, and no experimental studies were identified. Methodological shortcomings were common, especially the use of single-item nightmare assessment. Thirty-five studies assessed the path from nightmares to psychiatric symptoms. Depression (n = 10 studies), PTSD (n = 10) and anxiety (n = 5) were the most commonly assessed outcomes in trials. Most were not designed to assess the effect of nightmare treatment on psychiatric symptoms. Treating nightmares led to moderate reductions in PTSD and depression, small to moderate reductions in anxiety, and potentially moderate reductions in paranoia. Nightmares increased the risk of later suicide outcomes (n = 10), but two small pilot trials indicated that treating nightmares might potentially prevent recovery of suicidal ideation. PTSD treatment led to large reductions in trauma-related nightmares (n = 3). The limited literature suggests that treating nightmares may be one route to lessening threat-based disorders in particular, suggestive of a causal relationship. Overall, however, nightmares in most disorders are greatly understudied.
Replication competent retrovirus testing (RCR) in the National Gene Vector Biorepository: No evidence of RCR in 1,595 post-treatment peripheral blood samples obtained from 60 clinical trials
Authors: Kenneth Cornetta, Jing Yao, Kimberley House, Lisa Duffy, Prasad S. Adusumilli, Rachel Beyer, Claire Booth, Malcolm Brenner, Kevin Curran, Bambi Grilley, Helen Heslop, Christian S. Hinrichs, Rosandra N. Kaplan, Hans-Peter Kiem, James N. Kochenderfer, Donald B. Kohn, Sham Mailankody, Scott M. Norberg, Roisin E. O'Cearbhaill, Jennifer Pappas, Jae Park, Carlos Ramos, Antonio Ribas, Isabelle Rivière, Steven A. Rosenberg, Craig Sauter, Nirali N. Shah, Susan F. Slovin, Adrian Thrasher, David A. Williams, Tsai-Yu Lin
Journal: Molecular Therapy (2022)

The clinical impact of any therapy requires the product be safe and effective. Gammaretroviral vectors pose several unique risks, including inadvertent exposure to replication competent retrovirus (RCR) that can arise during vector manufacture. The US FDA has required patient monitoring for RCR, and the National Gene Vector Biorepository is an NIH resource that has assisted eligible investigators in meeting this requirement. To date, we have found no evidence of RCR in 338 pre-treatment and 1,595 post-treatment blood samples from 737 patients associated with 60 clinical trials. Most samples (75%) were obtained within 1 year of treatment, and samples as far out as 9 years after treatment were analyzed. The majority of trials (93%) were cancer immunotherapy, and 90% of the trials used vector products produced with the PG13 packaging cell line. The data presented here provide further evidence that current manufacturing methods generate RCR-free products and support the overall safety profile of retroviral gene therapy. The clinical impact of any therapy requires the product be safe and effective. Gammaretroviral vectors pose several unique risks, including inadvertent exposure to replication competent retrovirus (RCR) that can arise during vector manufacture. The US FDA has required patient monitoring for RCR, and the National Gene Vector Biorepository is an NIH resource that has assisted eligible investigators in meeting this requirement. To date, we have found no evidence of RCR in 338 pre-treatment and 1,595 post-treatment blood samples from 737 patients associated with 60 clinical trials. Most samples (75%) were obtained within 1 year of treatment, and samples as far out as 9 years after treatment were analyzed. The majority of trials (93%) were cancer immunotherapy, and 90% of the trials used vector products produced with the PG13 packaging cell line. The data presented here provide further evidence that current manufacturing methods generate RCR-free products and support the overall safety profile of retroviral gene therapy.
Delivering mRNA to Secondary Lymphoid Tissues by Phosphatidylserine‐Loaded Lipid Nanoparticles
Authors: Masaki Gomi, Yu Sakurai, Minami Sato, Hiroki Tanaka, Yumi Miyatake, Koichi Fujiwara, Mizuki Watanabe, Satoshi Shuto, Yuta Nakai, Kota Tange, Hiroto Hatakeyama, Hidetaka Akita
Journal: Advanced Healthcare Materials (2022)

Lipid nanoparticles (LNPs) are one of the most successful technologies in messenger RNA (mRNA) delivery. While the liver is the most frequent target for LNP delivery of mRNA, technologies for delivering mRNA molecules to extrahepatic tissues are also important. Herein, it is reported on the development of an LNP that targets secondary lymphoid tissues. New types of alcohol-soluble phosphatidylserine (PS) derivatives are designed as materials that target immune cells and then incorporated into LNPs using a microfluidic technique with a high degree of scalability and reproducibility. The resulting LNP that contained the synthesized PS delivered mRNA to the spleen much more efficiently compared to a control LNP. A sub-organ analysis revealed that the PS-loaded LNP is extensively taken up by tissue-resident macrophages in the red pulp and the marginal zone of the spleen. Thus, the PS-loaded LNP reported in this study will be a promising strategy for clinical applications that involve delivering mRNA to the spleen.
Association of 5α-Reductase Inhibitors With Dementia, Depression, and Suicide
Authors: Miguel Garcia-Argibay, Ayako Hiyoshi, Katja Fall, Scott Montgomery
Journal: JAMA Network Open (2022)

Importance In recent decades, there has been increased interest in the possible adverse neurological effects of 5α-reductase inhibitors (5-ARIs), which have been used mainly for benign prostatic hyperplasia and androgenic alopecia. Numerous studies and reports have indicated associations of 5-ARIs with depression and suicide. However, most of these studies had methodological shortcomings, and very little is known about the potential association of 5-ARIs with dementia. Objective To investigate the association of 5-ARI use with all-cause dementia, Alzheimer disease, vascular dementia, depression, and suicide. Design, Setting, and Participants This Swedish register-based cohort study included 2 236 876 men aged 50 to 90 years between July 1, 2005, and December 31, 2018. Statistical analyses were performed from September 15, 2021, to May 25, 2022. Main Outcomes and Measures A diagnosis of all-cause dementia, Alzheimer disease, vascular dementia, depression, or completed suicide. Exposures A recorded prescription in the Swedish national prescription register of finasteride or dutasteride and duration of use. Results Of 2 236 876 men (median age at the start of follow-up, 55 years [IQR, 50-65 years] and at treatment initiation, 73 years [IQR, 66-80 years]), 70 645 (3.2%) started finasteride treatment, and 8774 (0.4%) started dutasteride treatment. Men taking finasteride or dutasteride were at increased risk of all-cause dementia (finasteride: hazard ratio [HR], 1.22 [95% CI, 1.17-1.28]; dutasteride: HR, 1.10 [95% CI, 1.01-1.20]), Alzheimer disease (finasteride: HR, 1.20 [95% CI, 1.10-1.31]; dutasteride: HR, 1.28 [95% CI, 1.09-1.50]), vascular dementia (finasteride: HR, 1.44 [95% CI, 1.30-1.58]; dutasteride: HR, 1.31 [95% CI, 1.08-1.59]), and depression (finasteride: HR, 1.61 [95% CI, 1.48-1.75]; dutasteride: HR, 1.68 [95% CI, 1.43-1.96]). However, the magnitude of the association decreased over time, and the findings became statistically nonsignificant with continuous exposures over 4 years, except for depression, which showed a constant risk over time, with no differences between finasteride and dutasteride. In contrast, 5-ARIs were not associated with suicide (finasteride: HR, 1.22 [95% CI, 0.99-1.49]; dutasteride: HR, 0.98 [95% CI, 0.62-1.54]). Conclusions and Relevance This cohort study found that, while men receiving 5-ARI treatment showed a higher risk for dementia in the initial periods after starting treatment, the decreasing magnitude of the association over time suggested that the risk may be, entirely or in part, due to increased dementia detection among patients with benign prostate enlargement. Both finasteride and dutasteride were similarly associated with depression with a constant risk over time, while neither drug was associated with suicide. Prescribing clinicians and potential users should be aware of the possible risks for depression associated with 5-ARI use.
Cognitive change in breast cancer patients up to 2 years after diagnosis
Authors: Marie Lange, Sophie Lefevre Arbogast, Isabelle Hardy-Léger, Olivier Rigal, Johan Le Fel, Barbara Pistilli, Jean Petrucci, Christelle Lévy, Aurélie Capel, Charles Coutant, Laure Médeau, Florence Lerebours, Laurence Vanlemmens, Marine Brion, Emmanuelle Bourbouloux, Maxime Blain, Giulia Binarelli, Ines Vaz-Luis, Bénédicte Giffard, Ophélie Querel, Sibille Everhard, Fabrice André, Cécile Charles, Sarah Dauchy, Florence Joly
Journal: JNCI Journal of the National Cancer Institute (2022)

Using the large nationwide French, national, multicenter, prospective cancer and toxicities (CANTO) cohort, we assessed cognitive functioning change after cancer treatments in a subgroup of breast cancer (BC) patients.We included patients with newly diagnosed invasive stage I-III BC enrolled in the CANTO substudy focused on cognitive evaluation and healthy control women matched for age and education. Episodic and working memory, executive functions, processing speed, attention, self-report cognitive difficulties (SRCD), fatigue, anxiety and depression were assessed with neuropsychological tests and self-report questionnaires before treatment (baseline) and approximately 1 (year 1) and 2 years (year 2) after diagnosis. We used linear mixed models to study changes in cognition and tested the effect of adjuvant chemotherapy.We studied 276 localized BC patients (62% chemotherapy) compared with 135 healthy controls (HC). After adjustment, patients had lower baseline working memory, processing speed, and attention scores than HC (P ≤ .001), and the difference remained statistically significant over follow-up for working memory and processing speed. Executive function scores were similar between groups at baseline but decreased at year 1 among patients compared with HC (Pchange = .006). This decrease in chemotherapy patients was statistically significant compared with HC scores (Pchange < .001). After adjustment, SRCD were similar between BC patients and HC at baseline but increased in patients after treatment at year 1 (Pchange = .002).Cognitive difficulties are an important concern in BC patients, starting at diagnosis. Cancer treatments induce executive function decline and SRCD, which decrease over follow-up.
Population Genetic Considerations Regarding Evidence for Biased Mutation Rates in <i>Arabidopsis thaliana</i>
Authors: Brian Charlesworth, Jeffrey D Jensen
Journal: Molecular Biology and Evolution (2022)

Abstract It has recently been proposed that lower mutation rates in gene bodies compared with upstream and downstream sequences in Arabidopsis thaliana are the result of an “adaptive” modification of the rate of beneficial and deleterious mutations in these functional regions. This claim was based both on analyses of mutation accumulation lines and on population genomics data. Here, we show that several questionable assumptions were used in the population genomics analyses. In particular, we demonstrate that the difference between gene bodies and less selectively constrained sequences in the magnitude of Tajima's D can in principle be explained by the presence of sites subject to purifying selection and does not require lower mutation rates in regions experiencing selective constraints.
Factors associated with long-term use of digital devices in the electronic Framingham Heart Study
Authors: Chathurangi H. Pathiravasan, Yuankai Zhang, Xuzhi Wang, Ludovic Trinquart, Emelia J. Benjamin, Belinda Borrelli, David D. McManus, Vik Kheterpal, Honghuang Lin, Nicole L. Spartano, Eric Schramm, Chunyu Liu, Joanne M. Murabito
Journal: npj Digital Medicine (2022)

Long-term use of digital devices is critical for successful clinical or research use, but digital health studies are challenged by a rapid drop-off in participation. A nested e-cohort (eFHS) is embedded in the Framingham Heart Study and uses three system components: a new smartphone app, a digital blood pressure (BP) cuff, and a smartwatch. This study aims to identify factors associated with the use of individual eFHS system components over 1-year. Among 1948 eFHS enrollees, we examine participants who returned surveys within 90 days (n = 1918), and those who chose to use the smartwatch (n = 1243) and BP cuff (n = 1115). For each component, we investigate the same set of candidate predictors for usage and use generalized linear mixed models to select predictors (P < 0.1, P value from Z test statistic), adjusting for age, sex, and time (app use: 3-month period, device use: weekly). A multivariable model with the predictors selected from initial testing is used to identify factors associated with use of components (P < 0.05, P value from Z test statistic) adjusting for age, sex, and time. In multivariable models, older age is associated with higher use of all system components. Female sex and higher education levels are associated with higher completion of app-based surveys whereas higher scores for depressive symptoms, and lower than excellent self-rated health are associated with lower use of the smartwatch over the 12-month follow-up. Our findings show that sociodemographic and health related factors are significantly associated with long-term use of digital devices. Future research is needed to test interventional strategies focusing on these factors to evaluate improvement in long-term engagement.
Conformable neural interface based on off-stoichiometry thiol-ene-epoxy thermosets
Authors: Eleonora Borda, Danashi Imani Medagoda, Marta Jole Ildelfonsa Airaghi Leccardi, Elodie Geneviève Zollinger, Diego Ghezzi
Journal: Biomaterials (2022)

Off-stoichiometry thiol-ene-epoxy (OSTE+) thermosets show low permeability to gases and little absorption of dissolved molecules, allow direct low-temperature dry bonding without surface treatments, have a low Young's modulus, and can be manufactured via UV polymerisation. For these reasons, OSTE+ thermosets have recently gained attention for the rapid prototyping of microfluidic chips. Moreover, their compatibility with standard clean-room processes and outstanding mechanical properties make OSTE+ an excellent candidate as a novel material for neural implants. Here we exploit OSTE+ to manufacture a conformable multilayer micro-electrocorticography array with 16 platinum electrodes coated with platinum black. The mechanical properties allow conformability to curved surfaces such as the brain. The low permeability and strong adhesion between layers improve the stability of the device. Acute experiments in mice show the multimodal capacity of the array to record and stimulate the neural tissue by smoothly conforming to the mouse cortex. Devices are not cytotoxic, and immunohistochemistry stainings reveal only modest foreign body reaction after two and six weeks of chronic implantation. This work introduces OSTE+ as a promising material for implantable neural interfaces.
Incidence of Retinal Detachment, Macular Edema, and Ocular Hypertension after Neodymium:Yttrium-Aluminum-Garnet Capsulotomy
Authors: Corinne Dot, Cédric Schweitzer, Antoine Labbé, François Lignereux, Pascal Rozot, Mélanie Goguillot, Françoise Bugnard, Antoine P. Brézin
Journal: Ophthalmology (2022)
Biology-inspired data-driven quality control for scientific discovery in single-cell transcriptomics
Authors: Ayshwarya Subramanian, Mikhail Alperovich, Yiming Yang, Bo Li
Journal: Genome biology (2022)

Quality control (QC) of cells, a critical first step in single-cell RNA sequencing data analysis, has largely relied on arbitrarily fixed data-agnostic thresholds applied to QC metrics such as gene complexity and fraction of reads mapping to mitochondrial genes. The few existing data-driven approaches perform QC at the level of samples or studies without accounting for biological variation.
Clustering Deviation Index (CDI): a robust and accurate internal measure for evaluating scRNA-seq data clustering
Authors: Jiyuan Fang, Cliburn Chan, Kouros Owzar, Liuyang Wang, Diyuan Qin, Qi-Jing Li, Jichun Xie
Journal: Genome biology (2022)

Abstract Most single-cell RNA sequencing (scRNA-seq) analyses begin with cell clustering; thus, the clustering accuracy considerably impacts the validity of downstream analyses. In contrast with the abundance of clustering methods, the tools to assess the clustering accuracy are limited. We propose a new Clustering Deviation Index (CDI) that measures the deviation of any clustering label set from the observed single-cell data. We conduct in silico and experimental scRNA-seq studies to show that CDI can select the optimal clustering label set. As a result, CDI also informs the optimal tuning parameters for any given clustering method and the correct number of cluster components.
Characterization of multi-domain postoperative recovery trajectories after cardiac surgery using a digital platform
Authors: Makoto Mori, Sanket S. Dhruva, Arnar Geirsson, Harlan M. Krumholz
Journal: npj Digital Medicine (2022)

Abstract Understanding postoperative recovery is critical for guiding efforts to improve post-acute phase care. How recovery evolves during the first 30 days after cardiac surgery is not well-understood. A digital platform may enable granular quantification of recovery by frequently capturing patient-reported outcome measures (PROM) that can be clinically implemented to support recovery. We conduct a prospective cohort study using a digital platform to measure recovery after cardiac surgery using a PROM sent every 3 days for 30 days after surgery to characterize recovery in multiple domains (e.g., pain, sleep, activities of daily living, anxiety) and to identify factors related to the patient’s perception of overall recovery. We enroll patients who underwent cardiac surgery at a tertiary center between January 2019 and March 2020 and automatically deliver PROMs and reminders electronically. Of the 10 surveys delivered per patient, 8 (IQR 6–10) are completed. Patients who experienced postoperative complications more commonly belong to the worst overall recovery trajectory. Of the 12 domains modeled, only the worst anxiety trajectory is associated with the worse overall recovery trajectory membership, suggesting that even when patients struggle in the recovery of other domains, the patient may still feel progress in their recovery. We demonstrate that using a digital platform, automated PROM data collection, and characterization of multi-domain recovery trajectories is feasible and likely implementable in clinical practice. Overall recovery may be impacted by complications, while slow progress in constituent domains may still allow for the perception of overall recovery progression.
NOV03 for Dry Eye Disease Associated with Meibomian Gland Dysfunction
Authors: Joseph Tauber, Gregg J. Berdy, David L. Wirta, Sonja Krösser, Jason L. Vittitow, Louis M. Alpern, Carol Aune, Gregg J. Berdy, Johnathon Eric Downing, Sherif El-Harazi, David G. Evans, Damien Goldberg, Jack Greiner, Edward Holland, Mitchell A. Jackson, Gary W. Jerkins, Kathleen Kelley, Joseph Martel, Joseph L. Meyer, Theodore Pasquali, Matthew D. Paul, Bernard R. Perez, Edward R. Rashid, Kyle Rhodes, Jerry Robben, Philip Lee Shettle, Stephen E. Smith, Robert John Smyth-Medina, Joseph Tauber, David Wirta, Daniel V. Zimmer
Journal: Ophthalmology (2022)
Targeting proteostasis of the HEV replicase to combat infection in preclinical models
Authors: Fei Zhang, Ling-Dong Xu, Qian Zhang, Ailian Wang, Xinyuan Yu, Shengduo Liu, Chu Chen, Shiying Wu, Jianping Jin, Aifu Lin, Dante Neculai, Bin Zhao, Xin-Hua Feng, Tingbo Liang, Pinglong Xu, Yao-Wei Huang
Journal: Journal of Hepatology (2022)
Individuals heterozygous for ALG8 protein-truncating variants are at increased risk of a mild cystic kidney disease
Authors: Benjamin Apple, Gino Sartori, Bryn Moore, Kiran Chintam, Gurmukteshwar Singh, Prince Mohan Anand, Natasha T. Strande, Tooraj Mirshahi, William Triffo, Alexander R. Chang
Journal: Kidney International (2022)